The main thrust of this research program has been aimed at achieving a more detailed understanding of the relationships between hemoglobin structure and function (or in the case of mutants such as hemoglobin S, dysfunction). During the current year we have pursued this goal by 1) determining the structures of a number of interesting mutant hemoglobins, 2) studying the changes in the structure of hemoglobin produced by drugs of potential value in the treatment of sickle cell disease, and 3) initiating studies to determine the structure of isolated Beta chains. The work on mutant hemoglobins has resulted in direct structural evidence supporting a recent proposal by Perutz that the cooperative nature of oxygen binding in hemoglobin is due in part to a tension on the heme iron in deoxyhemoglobin. The X-ray studies of carbamyl and pyridoxal derivatives of hemoglobin have detected a possible correlation between changes in the structure of the modified Beta chain and the effect of these drugs on the propensity of hemoglobin S to gel. These studies have also revealed inorganic anion binding sites which may be physiologically important in regulating oxygen affinity and CO2 binding in vivo. BIBLIOGRAPHIC REFERENCE: Ten Eyck, L. F. and Arnone, A., "Three-dimensional Fourier Synthesis of Human Deoxyhemoglobin at 2.5 A Resolution," J. Mol. Biol. (1976) 100, 3-11.